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Ocular Inflammation

Ocular Inflammation

The Problem | Review of the literature | Integration | Conclusion | References

 

The Problem

It is well known that rosacea often affects not only the skin of the face, but also the eye. For a student of dermatology it is extremely difficult to understand the relationship between a papulopustular infundibulocentric dermatitis characterized histopathologically by inflammatory infiltrates in and around infundibula on one hand and keratitis and conjunctivitis on the other. In current textbooks of dermatology and dermatopathology, no clear concept about the pathogenetic link between both manifestations of the disease is provided.[1-6]

Search via Medline reveals more than 1000 articles devoted to rosacea, but most of those articles deal with clinical diagnosis and treatment of the condition, while only few present results of scientific investigations; rarely were pathophysiological, histopathological, immunohistochemical, immunofluorescence, and electronmicroscopic studies undertaken. Fewer than 80 of those articles are dedicated to the problem of involvement of the eye in rosacea: very few of them studied clinical signs and symptoms of ocular rosacea in a bigger group of patients.

This article presents the results of a comprehensive review of articles pertinent to the subject published in journals of ophthalmology and dermatology in the last decades. Then, an attempt is made to integrate all observations on the basis of what is known about anatomy and physiology of the eye and about clinical and histopathologic features of rosacea in the skin.

 

Review of the literature (Go to Top)

Fewer than 30 articles were identified that investigated and/or discussed pathogenetic mechanisms that might contribute to the clinical manifestation of so-called ocular rosacea.[7-32] While it is long known that rosacea may at times involve the eye, considerable confusion about the pathogenesis existed already in the beginning of the last century. A comprehensive work by Walker published in 1948 included a review of previous studies by various colleagues who had suggested that “digestive upsets” (Ryle and Berber 1920, Brown 1925, Eastwood 1928 and 34), “deficiency diseases” (Johnson and Eckard 1940, Sydenstricker, Sebrell, Cleckley and Kruse 1940, Johnson 1941, Fish 1943), and “hormonal disorders” (Zondek, Landau and Bromberg 1947) contributed to the development of rosacea keratitis. All these authors agreed that rosacea keratitis was a manifestation of a systemic metabolic diseases and not a local process.[7] Walker herself, however, studied 76 patients with ophthalmic rosacea, 50 of whom had signs of keratitis while 26 showed only blepharitis and conjunctivitis. Walker investigated the association of rosacea with allergies and found that 52 of her patients had signs of allergies. Therefore she concluded that rosacea keratitis is an allergic condition.[7]

Borrie, in 1953, noted blepharitis involving the Meibomian glands in nearly 100% of patients having rosacea,[8] while Jenkins et al., in 1979, found foreign body sensation, burning, superficial punctate erosions, chalazia, and blepharitis to be the most common signs of ocular rosacea.[9] The latter authors later studied systematically 75 patients with recurrent chalazia and noted 65% of them to have rosacea of the face clinically.[10] McCully and Sciallis, in two articles that appeared in 1977 and 1983,[11, 12] confirmed that patients with chronic blepharitis involving Meibomian glands often had rosacea of the face and they suggested that “a generalized sebaceous gland dysfunction that included the Meibomian glands” might be the explanation for the association of skin and eye symptoms in those patients. The authors concluded that “stagnation of the Meibomian glands presumably caused a defect in the tear lipid layer, this resulted in an unstable tear film that produced superficial punctate keratopathy.”

In 1981, Jester, Nicolaides, and Smith undertook a major study about histology of the Meibomian glands independently from the situation in rosacea; they pointed out the similarities and differences between Meibomian glands of the eyelids and sebaceous glands in the folliculosebaceous unit of the skin.[13] The authors postulated that “abnormalities of keratinization” may be responsible for what they called “Meibomian gland dysfunction.” These findings were confirmed by Gutgesell, Stern, and Hood, in 1982, who noted obstruction and dilatation of ducts, what they interpreted as squamous metaplasia, foreign body reaction, and granuloma formation in sections of tissue of patients who had what they called “severe Meibomian dysfunction” and were undergoing ectropium repair.[14]

In 1984, Lemp and coworkers studied 60 patients with ocular rosacea with Schirmer’s test and compared the results with those in healthy control subjects. The prevalence of dry eyes was significantly greater in the patients with rosacea. The authors hypothesized that “The coexistence of keratoconjunctivitis sicca and ocular rosacea probably causes a high level of symptoms that lead patients to examination.”[15] Robin et al., however, in 1985, supported the hypothesis that “dysfunction of Meibomian glands” might be an important factor in the pathogenesis of rosacea by in vivo transillumination biomicroscopy and they found marked distortion and loss of normal gland anatomy in patients with rosacea.[16]

Hoang-Xuang and coworkers investigated sections of tissue of epibulbar conjunctiva by immunofluorescence and immunohistochemistry; their results showed an increase of nearly all cell types in the conjunctiva of patients with rosacea, but especially of T-helper cells.[17] They concluded that “rosacea is primarily a skin disease and … that all the ocular lesions are secondary to the eyelid involvement”, but then they supposed that “a type IV hypersensitivity reaction [is] … the predominant immunologic mechanism accounting for the conjunctival inflammation in ocular rosacea.”

Gudmundsen et al., in 1992, suggested a connection between what he called “Meibomiasis” and the finding of dry eyes in patients with rosacea, averring that “If the outer lipid layer of the tear film, which is derived from Meibomian gland secretions, is abnormal in rosacea, then the tear film may become unstable with greater tendency to brake up and to evaporate, thereby resulting in dryness of the ocular surface.”[18] Occasionally extensive squamous hyperplasia of the Meibomian duct has been reported in rosacea.[19]

Zengin et al., in 1995, confirmed again that patients with what they diagnosed as “Meibomian gland dysfunction” and rosacea had a pathologic Schirmer test, that indicating that their tear film break-up time was significantly reduced; they suggested that “Meibomian gland dysfunction is an important feature in ocular rosacea.” [20] Driver and Lemp, in 1996, in their review about Meibomian gland dysfunction summarized that “Meibomian gland dysfunction is … an important form of blepharitis. … and frequently associated with dermatologic conditions such as acne rosacea.” And they continued to say that “Histopathologic studies suggest that hyperkeratinization is important in the pathogenesis of Meibomian gland dysfunction. Narrowing of the ductule lumen and desquamation of epithelial cells leads to glandular obstruction.”[21]

Akpek et al., also in 1996, examined more than 100 patients with rosacea involving the eye and found Meibomian gland dysfunction, telangiectasia, and irregularity of the lid margins to be the features encountered most often, whereas conjunctival hyperemia and keratoconjunctivitis sicca were by far less common.[22] Nevertheless the authors concluded that “none of the findings of ocular rosacea are specific.” Quarterman et al., in 1997, described erythema, telangiectasia, and Meibomian gland dysfunction, defined as inspissation, distortion, and plugging of Meibomian glands, as the most common sign of ocular rosacea.[23] Even though the authors stated that “Rosacea is a vascular disorder,” they added later that “it is interesting to speculate that Meibomian glands, a modified sebaceous gland of the eyelid, may play an important role in the disease.”

Barton et al., in 1997, studied the concentrations of IL-1a, and TNFa in the tears of patients with rosacea, they observed an elevation of IL-1a, but the relevance of these findings was not explained compellingly by the authors. In their comment they say that “it may form an important positive feedback mechanism that encourages tear stagnation and the perpetuation of ocular surface inflammation.”[24] Pisella, Brignole et al., in 2000, investigated the conjunctival epithelium by flow cytomeric analysis, they demonstrated an increase of HLA-DR and ICAM-1 and confirmed previous findings that Schirmer test was significantly decreased in patients with rosacea.[25] The authors claimed that “the cause of ocular irritation in patients with rosacea has not yet been established” and they propose that their results confirm that “rosacea is most likely a consequence of chronic ocular surface disease.”

In 2001,Yaylali and Ozyurt published a major study on ophthalmic rosacea that was undertaken to evaluate the significance of tear function tests in the disease.[26] The authors confirmed that patients with rosacea often complain about dry eyes that can be measured objectively by Schirmer test. Additionally they recognized that the most frequent clinical finding in ophthalmic rosacea was what they considered to be Meibomitis; it was noted in more than 90 % of the patients. All other findings like telangiectasis, blepharitis, and keratopathy were noted less often. The authors realized that “most ocular symptoms [in rosacea] are related to dry eye” and that “meibomian dysfunction … may aggravate the clinical findings of the ocular disease in rosacea” but they did not interpret their findings in a pathogenetic point of view.

In 2004, Bron and Tiffany reviewed the current conceptions and hypotheses about the pathogenesis of tear film alterations and their consequences. They emphasized that a “lipid layer is the major barrier to evaporation from the ocular surface.” In their opinion, a decrease in its thickness was likely to cause evaporative dry eye. They considered “obstructive meibomian gland dysfunction” to be the most common cause of the evaporative dry eye and mentioned that this condition occurs as a primary disorder or secondary to rosacea, seborrheic or atopic dermatitis, and with cicatrizing conjunctival disorders, such as trachoma, erythema multiforme, and cicatricial pemphigoid.[27]

As recently as 2007, Baudouin attempted to clarify the pathogenesis of diseases associated with a dry eye and stated that many different diseases could cause tear film impairment and ocular surface damage, by tear instability and evaporation, tear hyposecretion, or both. In his opinion, “tear film instability/imbalance can be considered as the key point of dry eye disease.” He also mentioned that what he called Meibomian gland dysfunction as well as lipidic changes influenced tear film stability directly facilitating tear evaporation.[28]

Articles about rosacea in the literature of dermatology, however, usually make no mention of pathophysiologic considerations in regard to ocular rosacea as they were published in the literature of ophthalmology. Wilkin, in 1994, stated that “Ocular rosacea is principally vascular and correlates with the severity of flushing.” [29] Tanzi and Weinberg, in 2001, also stated that “the ocular manifestations of rosacea are commonly nonspecific and variable. The etiology of the inflammation is unknown and there is no diagnostic test for the disease.”[30]

Michel and colleagues, in 2003, found only 6% of patients with cutaneous rosacea to have involvement of the eye; [31] the severity of the ocular damage did not correlated with the stage of cutaneous involvement. Ghanem et al., however, emphasized in his investigation on the prevalence of ocular signs in acne rosacea that dermatologists were not as skilled to recognize involvement of the eye compared with ophthalmologists and that this doubtlessly affected the assessment of incidence of ocular rosacea if only charts of dermatology patients were reviewed.[32]

In a review article undertaken in 2004 by Stone and Chodos, the authors remarked that comparatively few papers on ocular rosacea have been published recently and that those on the pathogenesis of ocular rosacea focused on the role of bacterial lipases, and interleukin-1alpha and matrix metalloproteinases in the blepharitis and corneal epitheliopathy, respectively.[33] In a review article on Ocular rosacea that appeared in 2005, Alvarenga and Mannis suggested that “an altered inflammatory response plays an important role in both cutaneous and ocular rosacea.”[34]

Recently, special attention has been given to involvement of the eye in children with rosacea. A study by Nazir et al., in 2004, on ocular rosacea in childhood revealed that eyelid telangiectases and what he called “Meibomian gland disease” were the most common findings in these patients.[35] Cetinkaya and Akova, in 2006, studied four patients with ocular rosacea in pediatric patients and found Meibomitis, blepharitis, conjunctival hyperemia, and punctuate epitheliopathy to be present commonly.[36] In 2008, Chamaillard et al. studied cutaneous and ocular signs of childhood rosacea and found that among the ophthalmologic manifestations, chalazions and blepharoconjunctivitis were the main presenting symptoms.[37]

In sum, blepharitis, Meibomitis, so-called Meibomian dysfunction and keratoconjunctivitis sicca are the changes mentioned most often in patients with ocular rosacea who are described in the literature of ophthalmology. Sicca syndrome can be demonstrated by Schirmer test. Meibomitis is diagnosed clinically by the presence of papules and pustules at the ostia of Meibomian glands at the lid margin. Meibomian gland dysfunction is a hypothesis rather than a clinical diagnosis. No method is available yet to demonstrate objectively that the gland itself plays a role pathogenetically. The only features demonstrated repeatedly by way of clinical and microscopic examination of the eyelid is alterations of the duct of Meibomian glands which was said to be distorted, plugged, and exhibiting squamous differentiation. Histopathologic changes of rosacea of the eyelid do not exist, but it is interesting that just as in many biopsies taken from patients with rosacea, granuloma formation has been observed in patients with so-called Meibomian dysfunction.

Special investigations applying methods of immunology and immunohistochemistry have not contributed much to the understanding of clinical symptoms in patients with this condition.

Similarities of rosacea of the skin and the eye are addressed rarely, and the pathogenetic considerations in regard to rosacea of the eye made by ophthalmologists mostly did not find entry into the literature of dermatology. Only few authors took under consideration that rosacea of the eye is primarily rosacea of the eyelid and that changes of the disease in both places might be essentially the same. On the eyelids of patients with rosacea, the openings of Meibomian glands were often found to show inflammation and plugging. Some authors suggested that inflammation of Meibomian glands followed by Meibomian gland dysfunction could be responsible for conjunctivitis sicca in patients with ocular rosacea, because the secretion of Meibomian glands is considered to contribute to the outer lipid layer of the tear film, it thereby protecting form evaporation.

Even in the most recent publications about ocular rosacea, considerations about pathophysiological connections between all signs and symptoms of patients with rosacea are sparse and there is no uniformly accepted explanation of the association of symptoms of the skin and the eye.

 

Integration (Go to Top)

Rosacea of the skin

Rosacea of the skin is characterized clinically by erythema, telangiectases, papules, and pustules, which are located mostly on the face. Often lesions appear in the middle of the face and are accompanied by telangiectases. On sites other than the midface like forehead, perioral, and periocular regions, however, erythematous papules and papulopustules may be unaccompanied by telangiectases. In contrast to acne, patients with rosacea have no comedones. Histopathologically the papules and pustules are characterized by peri-infundibular, and intra-infundibular infiltrates that, at the outset of the disease, contain lymphocytes joined by spongiosis of infundibula,[38, 39] followed by neutrophils forming intra-infundibular pustules. Only later, plasma cells and histiocytes appear, the latter often forming granulomas as a consequence of rupture of infundibula and as a “foreign body response” to contents of infundibula spilled into the dermis. In short, the infundibula seem to play a key role in rosacea. Consequently, analogous structures should be the focus of interest in order to understand the situation of rosacea affecting the eye. To what extent sebaceous glands are involved in the pathogenesis of rosacea is not known. Rarely, however, are infiltrates of inflammatory cells seen in sebaceous lobular epithelium in lesions of rosacea, making it unlikely that they are quintessential pathogenetically. Moreover, rosacea also appears at times in prepubescent children in whom sebaceous glands are not yet developed, only immature mantles being found around follicles.

Anatomy and pathology of the eyelid

The skin of the eyelid is basically identical to the skin of the rest of the face (Fig. 1). At the lid margin, the keratinized epidermis blends with a mucous membrane, the conjunctiva. Between the epithelial layers of the eyelid a connective tissue is situated that contains muscle, collagen fibers, glands, and follicles. At the free margin of the lid the hair follicles of the eyelashes are positioned; these follicles are identical to those elsewhere in the skin but they lack the arrector pili muscle. The sebaceous glands around these follicles are called the Zeiss glands and, just as in any other hair follicle, these sebaceous glands enter at the junction of the infundibulum and the isthmus. The musculus orbicularis oculi, a skeletal muscle, is situated in the subcutaneous tissue of the eyelid in front of the tarsus, a fibrous plate that gives form and stability to the eyelid. Between the tarsus and the conjunctiva the Meibomian glands, which are also called the tarsal glands of the eyelid, are located. They are disposed in a plane vertically oriented to the lid margin, the glandular alveoli being connected by short lateral ducts to a long excretory duct with a stratified squamous epithelium. The ducts of those glands open to the inner free margin of the lid at the junction of skin and conjunctiva through channels that show infundibular differentiation marked by keratohyalin granules. While conventionally the Meibomian glands are considered to be unassociated with hair follicles, they must derive from a infundibulo-folliculo-apocrine-sebaceous germ jus as any other sebaceous gland because in one pathologic condition, so-called distichiasis, small hairs grow out of every opening of a Meibomian gland. In a healthy condition, however, the follicle as well as apocrine gland do not develop while sebaceous glands and infundibula form fully.

Fig. 1: Schema of the anatomy of the eye lid. A: Meibomian glands. B: Opening of Meibomian glands to the lid margins. C: Hair follicle of an eye lash. D: Sebaceous glands associated with eye lash follicles (Zeiss glands). F. Infundibula of eye lash follicles. G: eye lash. H: Vellus follicles with the sebaceous glands on the skin of the eye lid. I: Infundibula of vellus follciles at the eye lid. J: Vellus hair on the eye lid. K: Muscle. L: Tarsus. M: Tarsal part of the conjunctiva.

The tear film

The precorneal tear film (Fig. 2) consists of three layers that are produced by different glands. The outermost lipid layer measures approximately 100 nm in thickness. It is produced by the Meibomian glands and consists of cholesterol, cholesterol esters, triglycerides, and phospholipids. The Meibomian glands are sebaceous glands and, just as all sebaceous glands, they produce a lipophilic secretion very similar to sebum. The intermediate layer consists of a watery fluid containing electrolytes, glucose, and proteins manufactured by the lachrymal gland. The lachrymal gland is an exocrine gland located in the upper lateral orbita, which manufactures the tear fluid. The innermost mucoid layer has a thickness of 30 to 40μm and is produced by the accessory glands positioned in the eyelid as well as by the goblet cells of the conjunctiva. Approximately 1.5 μl of tear fluid are produced per minute and are distributed on the cornea by the eye lid movement. Approximately 10 to 15% of the tear film are exchanged per minute. The tear fluid is drained through the tear-nose channel. The secretion of Zeiss glands, the sebaceous glands associated with the eye lash follicles, also contributes to the stability of the tear film as their fatty sebaceous secretion envelops the eye lashes, which hold the tear film on the cornea.

Fig. 2: Schema of the precorneal tear film. 1: Outer lipid layer. 2: Intermediate watery layer. 3: Inner mucinous layer. 4: Epithelium of the cornea.

The tear film has a thickness of approximately 7-9 μm and an evaporation rate of 0.06 μl/cm2 per minute. It contributes to the nutrition of the cornea which is devoid of blood vessels and nourished only by way of diffusion. It also is essential to the optical function of the eye.

A pathologic condition of the eye manifests itself as a so-called “dry eye,” a “sicca syndrome.” In that circumstance, the tear film breaks. Consequently, the cornea is malnourished and becomes more susceptible to irritation and infection. Multiple causes may lead to such a state of a dry eye, e.g., the production of tears by the lachrymal gland may be reduced such as it is the case in Sjögren syndrome, or tears cannot be held by the eye lid because of an ectropium. As a consequence of both of these conditions, patients may experience similar complications such as conjunctivitis and keratitis.

The sicca syndrome can be measured by way of the Schirmer test. The stability of the tear film can be investigated with fluorescent colors and split lamp examination of the eye.

The cornea

The cornea is a an avascular tissue with very few cells but prominent innervation (Fig. 3). The nutrition of the cornea is by way of diffusion from the precorneal tear film, the chamber fluid, and the vascularization at the margin. The cornea consists of several layers, from outside to inside: epithelium, Bowman membrane, stroma, Descemet membrane, and endothelium.

Fig. 3: The cornea. A: Precorneal tear film. B: Epithelium. C: Bowman membrane. D: Stroma. E: Descemet membrane. F: Endothelium.

Confusing terms

Blepharitis: Inflammation of the eye lid. The term is not specific as various types of inflammatory processes can cause inflammation of the eye lid among them being conditions as diverse as rosacea, allergic contact dermatitis, cicatricial pemphigoid, and herpetic infection. In regard to rosacea, blepharitis is often used as a synonym to Meibomitis (see below).

Meibomitis: Inflammation of the Meibomian gland. Strictly, this diagnosis should only be made by way of histopathology when infiltrates of inflammatory cells are found within the sebaceous lobules of the Meibomian gland in the eye lid. Rarely, however, are histopathologic studies undertaken of the eyelid. Mostly the term Meibomitis is used as a clinical term when inflammation is seen at the lid margin centered around the openings of the Meibomian glands. Some authors observed also plugging of Meibomian ducts with corneocytes and suggested that squamous metaplasia may be a sign of Meibomitis.

Meibomian (gland) dysfunction: Not clearly defined. This term has been used to designate pathologic conditions of the Meibomian glands and/or ducts which are typified by a decreased secretion. In such conditions, the outermost lipid layer of the tear film is reduced and the tear film breaks, which is one of the reasons for a “dry eye,” the so-called sicca syndrome (see below).

“Sicca syndrome”: A reduced tear film. Strictly speaking, the “sicca syndrome” is not a syndrome but a clinical finding. The reduction of the tear film can be measured by the Schirmer test and patients complain about dry eyes. The reasons for a reduction in the tear film are many and may affect any of the layers of the tear film. The most well known reason is reduced secretion of the lachrymal gland in Sjögren syndrome, but impaired secretion of Meibomian glands also causes the same clinical finding of a dry eye because the watery layer of the tear film evaporates more easily when not sufficiently protected by an outermost lipid layer manufactured by Meibomian glands.

Keratitis: This term means strictly speaking “inflammation of the cornea,” but inflammation requires vascularization and infiltrates of inflammatory cells. As an avascular tissue such as the cornea cannot develop true inflammation but only infiltrates of inflammatory cells. Moreover, the diagnosis of keratitis is usually a clinical diagnosis and not a histopathologic diagnosis. What is referred to as “keratitis” consists of defects in the cornea. Defects can be superficial, affecting only the outermost epithelium, or be deep and even, penetrating the cornea. When ulceration develops, it is usually followed by infiltrates of inflammatory cells. Fluorescent colors can be used to demonstrate ulceration of the cornea in a split lamp examination of the eye. The reasons leading to ulceration of the cornea are far reaching from traumatic to infectious. One reason for ulceration of the cornea is malnutrition when the tear film is not intact. Such defects of the cornea are the common end pathway of any disease associated with a reduced tear film (see above). Keratitis is almost always accompanied by conjunctivitis, i.e., dilation of vessels and inflammatory infiltrates in the conjunctiva.

Hypothesis about the pathogenesis of ocular rosacea

It is likely that the same pathologic process that causes rosacea on the face is also responsible for rosacea on the eye (Figs. 3-5). The corresponding structure between the eye and the skin of the face is the eye lid. Essentially, the eye lid is nothing else but skin with a few anatomic alterations. On the face, the most consistent finding in lesions of rosacea is inflammation in and around the infundibula. On the eye lid, infundibula exist at the hair follicles of the eye lashes, the Zeiss glands, but also Meibomian glands enter to the eye lid margin through channels that are identical in differentiation to infundibula. These channels have a squamous epithelium just as the infundibula, a finding that by some authors has been misinterpreted as “squamous metaplasia.” Infiltrates in and around these epithelial funnels are responsible for the key feature of “ocular rosacea,” namely, blepharitis. In rosacea, blepharitis starts typically at the ostia of eye lashes and Meibomian glands. Sometimes, even pustulation can be seen at the eye lid margin.

Fig. 4: A patient diagnosed with rosacea of the face. A: A pustule on the lower eyelid represents involvement of the Meibomian duct in the process of rosacea. B: Conjunctivitis with dilation of vessels. C: Erythematous papule on the upper lid showing rosacea involving the infundibla of vellus follicles on the eye lid skin.

Fig. 5: A patient diagnosed with rosacea of the face. A: Pustules on the upper eye lid showing rosacea involving the infundibla of vellus follicles on the eye lid skin. B: Pustules at the lid margin of the lower eyelid represent involvement of the Meibomian duct in the process of rosacea. They are present together with conjunctivitis.

But how can involvement of the cornea in rosacea be explained when infundibula are completely absent there? What is the connection between “blepharitis” on one hand and “keratitis” on the other? The answer resides in the observation that patients with rosacea often have a pathologic Schirmer test, a so-called dry eye. A dry eye develops consequent to an imbalance of the tear film. Since the lachrymal gland is entirely uninvolved in the process of rosacea, the role that Zeiss and Moll glands play in the stability of the tear film is crucial to the understanding of the process. When infundibula of eye lashes and infundibular channels of Meibomian glands are affected by the process of rosacea, the secretion of those glands may be impaired causing a thinning of the outermost lipid layer of the tear film. If that layer is diminished, the watery layer of the tear film is more likely to evaporate. What follows is a common end pathway to any diseases that causes a reduced tear film, from Sjögren syndrome over ectropium to rosacea. If the tear film is broken for a longer period of time, defects will develop in the cornea because the nutrition of the cornea is impaired. Such a keratitis sicca is always accompanied by conjunctivitis and is usually referred to as “keratoconjunctivitis sicca.”

 

Conclusion (Go to Top)

In rosacea, the pathologic process of lesions on the face seems to be the very same that accounts, at least indirectly, for all the different manifestations of the disease at the eye. They are a consequence of inflammation in and around infundibula of the eye lashes as well as of the infundibula-like funnels that connect Meibomian glands with the lid margin. McCully and Sciallis, in two articles that appeared in 1977 and 1983 were the first to suggest a connection between blepharitis involving openings of Meibomian glands and a reduced tear film. Lemp and coworkers demonstrated in 1984 that a reduced tear film is found in many patients with rosacea of the eye. Gudmundsen et al., in 1992, stated clearly that a connection existed between inflammation at the openings of Meibomian glands and the finding of “dry eye” in patients with rosacea because the lipid layer of the tear film is reduced and the film breaks. Ulceration of the cornea (“keratitis”) in rosacea develops only consequent to the broken tear film and is accompanied by conjunctivitis. These changes are not specific for rosacea but may develop in any condition that reduces the tear film markedly. It is therefore not surprising that the most common manifestation of rosacea of the eye is blepharitis, the second most common is a “dry eye,” and only rarely, the full picture of keratitis develops. If keratitis develops, patients also will complain about photophobia and in time, vision will be impaired.

From the finding of a “dry eye” alone, it cannot be inferred that a patient has rosacea and neither can it from conjunctivitis and keratitis. Only the association with typical infundibulocentric inflammation on the eyelid margin allows a diagnosis to be made with specificity, especially when the rest of the face also shows lesions diagnostic of rosacea.

Despite the considerable effort made in the research of ophthalmology to the understanding of rosacea of the eye, little of it has found entry in the literature of dermatology. Some of the confusion in the literature of ophthalmology results from imprecise terminology, but there is also poor correlation with rosacea when it affects the skin of the rest of the face. Rosacea serves as a good example for showing that it is worthwhile to approach diseases of the skin from an interdisciplinary perspective.

Note: This article first appeared in Dermatopathology: Practical & Conceptual 2008;14(3):7.

 

References (Go to Top)

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